The long term objectives of this proposal are (1) To elucidate the natural history and mechanism of oncogenesis by herpesvirus using the Lucke tumor as a model system. (2) To gain an understanding at the molecular level of viral and cellular regulatory mechanisms using frog virus 3 (FV 3) as a model system. We will continue our search for a susceptible in vitro cell system for propagation and in vitro assay of the Lucke herpesvirus (LHV). Depending on success in achieving this goal we will characterize LHV physically, chemically, immunologically, and in its interaction with host cells in vitro and in vivo leading to virus replication and/or malignant trasformation. Special emphasis will be placed on the role environment plays in LHV-host cell interactions. The papova-like virus isolated from Luche tumors will be characterized further and attempts will be made to establish a transplantable Lucke tumor. FV 3 studies will be concernedwith isolation and characterization of virion structural proteins and determination of their functions. The mechanism of FV 3 inhibition or permissiveness of heterologous viral nucleic acid synthesis (e.g., VSV, Sindbis virus) in co-infected cells will be determined. Transcriptional and translational regulation of FV 3 gene expression in FV 3 infected cells will be analyzed. Further characterization will be made of FV 3 lipid composition, its origin and function. Additional ts mutants will be isolated, characterized, and used to help identify viral gene functions related to the above described studies on FV 3. Methods o be used include standard virological, biochemical, and immunological ones, as well as molecular hybridization and cell-free systems of transcription and protein synthesis.